Ashani Weeraratna Lab
Studying how cancer cells move to distant sites and how changes in the cells around a tumor impact that movement
About the Weeraratna Lab
The Weeraratna Laboratory focuses on trying to unravel the molecular mechanisms that lead to metastatic progression and therapy resistance. We are particularly interested in how aging governs tumor progression, and aim to identify age-related differences in responses to both targeted- and immunotherapy that can translate to improved clinical practices and outcomes for patients. We strive to create a diverse environment where everyone can thrive.
Research Overview
Our lab was one of the first to study how the aging microenvironment guides metastasis and therapy resistance in melanoma. Our studies encompass biophysical changes in the extracellular matrix and UV-induced premature aging that affect immune cell recruitment, tumor cell migration, and angiogenesis, including in distal microenvironments such as the lung and brain. We analyze how vasculature integrity dictates metastatic routes to these sites and how secreted factors drive metastatic signaling and therapy response. Through global analysis of the aged microenvironment using skin fibroblasts from donors of different ages, proteomics, and animal models, we study metastatic crosstalk at distal sites. The clinical implications may change practice, as we uncover age-related differences in responses to targeted- and immunotherapy. Our proteomics data guide research on how the aging primary immune landscape affects tumor dormancy and metabolism, including ferroptosis.
Cancer Invasion in 3D
Melanoma cells can undergo "phenotype switching" where they shift from a proliferating state to an invasive state. One method our lab uses to understand this switch is a spheroid invasion assay. We seed melanoma cells into a medium that causes them to grow into three-dimensional spheroid clusters. We then embed these spheroids into a collagen matrix and monitor how well the cells invade the surrounding collagen. We can view their physical spread, as in the brightfield images on the top row, and we can use staining to look at other aspects, like the live-dead cell staining in the bottom row. We can test the effect of variables such as the density of the collagen or the addition of chemicals on the invasion behavior. Here, cells in lower density collagen (left) are able to easily invade the surrounding collagen where many die, while at increasing density, fewer cells invade.
Selected Publications
Chhabra Y, Fane ME, Pramod S, Hüser L, Zabransky DJ, Wang V, Dixit A, Zhao R, Kumah E, Brezka ML, Truskowski K, Nandi A, Marino-Bravante GE, Carey AE, Gour N, Maranto DA, Rocha MR, Harper EI, Ruiz J, Lipson EJ, Jaffee EM, Bibee K, Sunshine JC, Ji H, Weeraratna AT. Sex-dependent effects in the aged melanoma tumor microenvironment influence invasion and resistance to targeted therapy. Cell, 2024.
Marino-Bravante GE, Carey AE, Hüser L, Dixit A, Wang V, Kaur A, Liu Y, Ding S, Schnellmann R, Gerecht S, Gu L, Eisinger-Mathason TSK, Chhabra Y, Weeraratna AT. Age-dependent loss of HAPLN1 erodes vascular integrity via indirect upregulation of endothelial ICAM1 in melanoma. Nature Aging, 2024.
Fane ME, Chhabra Y, Alicea GM, Maranto DA, Douglass SM, Webster MR, Rebecca VW, Marino GE, Almeida F, Ecker BL, Zabransky DJ, Hüser L, Beer T, Tang HY, Kossenkov A, Herlyn M, Speicher DW, Xu W, Xu X, Jaffee EM, Aguirre-Ghiso JA, Weeraratna AT. Stromal changes in the aged lung induce an emergence from melanoma dormancy. Nature, 2022.
Douglass SM, Fane ME, Sanseviero E, Ecker BL, Kugel CH 3rd, Behera R, Kumar V, Tcyganov EN, Yin X, Liu Q, Chhabra Y, Alicea GM, Kuruvilla R, Gabrilovich DI, Weeraratna AT. Myeloid-Derived Suppressor Cells Are a Major Source of Wnt5A in the Melanoma Microenvironment and Depend on Wnt5A for Full Suppressive Activity. Cancer Research, 2021.
Alicea GM, Rebecca VW, Goldman AR, Fane ME, Douglass SM, Behera R, Webster MR, Kugel CH, Ecker BL, Caino MC, Kossenkov AV, Tang HY, Frederick DT, Flaherty KT, Xu X, Liu Q, Gabrilovich DI, Herlyn M, Blair IA, Schug ZT, Speicher DW, Weeraratna AT. Changes in Aged Fibroblast Lipid Metabolism Induce Age-dependent Melanoma Cell Resistance to Targeted Therapy Via the Fatty Acid Transporter FATP2. Cancer Discovery, 2020.
Fane M, Weeraratna AT. How the ageing microenvironment influences tumour progression. Nature Reviews Cancer, 2020.
How to Join the Weeraratna Lab
Weeraratna Lab members join us from many pathways. Common ways to join the Lab are below.
PhD Students
The Weeraratna Lab is part of following PhD training programs at Johns Hopkins University. Visit the websites below to learn more about each program and how to apply. All programs provide full tuition and stipend support.
Master's Students
The Weeraratna Lab hosts students from the Department of Biochemistry and Molecular Biology Master of Health Science and Master of Science programs.
Undergraduate Students
The Weeraratna Lab hosts undergraduates from a variety of programs. If you are interested in joining the Weeraratna Lab as an undergraduate, please email Ashani Weeraratna.
Postdoctoral Fellows
To apply to work as a postdoctoral fellow in the Weeraratna Lab, email your CV and references to Ashani Weeraratna. In addition to training within our lab, the Biochemistry and Molecular Biology Department has an active postdoctoral training program.